Importance of Accurate Charges in Binding Affinity Calculations: A Case of Neuraminidase Series

Park, Kichul,Sung, Nack Kyun,Cho, Art E. Korean Chemical Society 2013 Bulletin of the Korean Chemical Society Vol.34 No.2

It has been shown that calculating atomic charges using quantum mechanical level theory greatly improves the accuracy of docking. A protocol was developed and shown to be effective. That this protocol works is just a manifestation of the fact that electrostatic interactions are important in protein-ligand binding. In order to investigate how the same protocol helps in prediction of binding affinities, we took a series of known cocrystal structures of influenza neuraminidase inhibitors with the receptor and performed docking with Glide SP, Glide XP, and QPLD, the last being a workflow that incorporates QM/MM calculations to replace the fixed atomic charges of force fields with quantum mechanically recalculated ones at a given docking pose, and predicted the binding affinities of each cocrystal. The correlation with experimental binding affinities considerably improved with QPLD compared to Glide SP/XP yielding $r^2$ = 0.83. The results suggest that for binding sites, such as that of neuraminidase, which are laden with hydrophilic residues, protocols such as QPLD which utilizes QM-based atomic charges can better predict the binding affinities.

Importance of Accurate Charges in Binding Affinity Calculations: A Case of Neuraminidase Series

Kichul Park,성낙균,조은성 대한화학회 2013 Bulletin of the Korean Chemical Society Vol.34 No.2

It has been shown that calculating atomic charges using quantum mechanical level theory greatly improves the accuracy of docking. A protocol was developed and shown to be effective. That this protocol works is just a manifestation of the fact that electrostatic interactions are important in protein-ligand binding. In order to investigate how the same protocol helps in prediction of binding affinities, we took a series of known cocrystal structures of influenza neuraminidase inhibitors with the receptor and performed docking with Glide SP, Glide XP, and QPLD, the last being a workflow that incorporates QM/MM calculations to replace the fixed atomic charges of force fields with quantum mechanically recalculated ones at a given docking pose, and predicted the binding affinities of each cocrystal. The correlation with experimental binding affinities considerably improved with QPLD compared to Glide SP/XP yielding r2 = 0.83. The results suggest that for binding sites, such as that of neuraminidase, which are laden with hydrophilic residues, protocols such as QPLD which utilizes QM-based atomic charges can better predict the binding affinities.

Hand-manageable graphene sticker for ultrafast mode-locked fiber lasers.

Park, Jaehyun,Park, Kichul,Spoor, Daniel,Hall, Benjamin,Song, Yong-Won Optical Society of America 2015 Optics express Vol.23 No.6

<P>We have developed a graphene sticker prepared by simply detaching graphene directly grown on a self-catalytic 관-Al???O??? substrate with a spin-coated polymer film. Our scheme is highlighted by the metal-free and bare-hand manageable process. The sticker is attached onto the flat surface of a D-shaped fiber to demonstrate an efficient fiber mode-locked laser. The 1-ps output pluses have the center wavelength, spectral width, and repetition rate of 1558.2 nm, 5.42 nm, and 4.77 MHz, respectively.</P>

Two-year clinical outcomes after discontinuation of long-term golimumab therapy in Korean patients with rheumatoid arthritis

Kichul Shin,Hyun Mi Kwon,Min Jung Kim,Myung Jae Yoon,Hyun Gyung Chai,Seong-Wook Kang,Won Park,Sung-Hwan Park,Chang-Hee Suh,Hyun Ah Kim,Seung-Geun Lee,Choong Ki Lee,배상철,Yong-Beom Park,Yeong Wook Song 대한내과학회 2022 The Korean Journal of Internal Medicine Vol.37 No.5

Background/Aims: The aim of this study was to investigate long-term post-discontinuation outcomes in patients with rheumatoid arthritis (RA) who had been treated with tumor necrosis factor-α inhibitors (TNF-αi) which was then discontinued. Methods: Sixty Korean patients with RA who participated in a 5-year GO-BEFORE and GO-FORWARD extension trials were included in this retrospective study. Golimumab was deliberately discontinued after the extension study (baseline). Patients were then followed by their rheumatologists. We reviewed their medical records for 2 years (max 28 months) following golimumab discontinuation. Patients were divided into a maintained benefit (MB) group and a loss-of-benefit (LB) group based on treatment pattern after golimumab discontinuation. The LB group included patients whose conventional disease-modifying antirheumatic drug(s) were stepped-up or added/switched (SC) and those who restarted biologic therapy (RB). Results: The mean age of patients at baseline was 56.5 years and 55 (91.7%) were females. At the end of follow-up, 23 (38.3%) patients remained in the MB group. In the LB group, 75.7% and 24.3% were assigned into SC and RB subgroups, respectively. Fifty percent of patients lost MB after 23.3 months. Demographics and clinical variables at baseline were comparable between MB and LB groups except for age, C-reactive protein level, and corticosteroid use. Restarting biologic therapy was associated with swollen joint count (adjusted hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.01 to 3.55) and disease duration (adjusted HR, 1.12; 95% CI, 1.02 to 1.23) at baseline. Conclusions: Treatment strategies after discontinuing TNF-αi are needed to better maintain disease control and quality of life of patients with RA.

Dynamic Changes in Helicobacter pylori Status Following Gastric Cancer Surgery

( Kichul Yoon ),( Nayoung Kim ),( Jaeyeon Kim ),( Jung Won Lee ),( Hye Seung Lee ),( Jong-chan Lee ),( Hyuk Yoon ),( Cheol Min Shin ),( Young Soo Park ),( Sang-hoon Ahn ),( Do Joong Park ),( Hyung Ho 대한소화기학회 2017 Gut and Liver Vol.11 No.2

Background/Aims: Helicobacter pylori eradication is recom-mended in patients with early gastric cancer. However, the possibility of spontaneous regression raises a question for clinicians about the need for “retesting” postoperative H. py-lori status. Methods: Patients who underwent curative gas-trectomy at Seoul National University Bundang Hospital and had a positive H. pylori status without eradication therapy at the time of gastric cancer diagnosis were prospectively enrolled in this study. H. pylori status and atrophic gastritis (AG) and intestinal metaplasia (IM) histologic status were as-sessed pre- and postoperatively. Results: One hundred forty patients (mean age, 59.0 years; 60.7% male) underwent subtotal gastrectomy with B-I (65.0%), B-II (27.1%), Roux-en-Y (4.3%), jejunal interposition (0.7%), or proximal gastrectomy (4.3%). Preoperative presence of AG (62.9%) and IM (72.9%) was confirmed. The mean period between surgery and the last endoscopic follow-up was 38.0±25.6 months. Of the 140 patients, 80 (57.1%) were found to be persistently posi-tive for H. pylori, and 60 (42.9%) showed spontaneous nega-tive conversion at least once during follow-up. Of these 60 patients, eight (13.3%) showed more complex postoperative dynamic changes between negative and positive results. The spontaneous negative conversion group showed a trend of having more postoperative IM compared to the persistent H. pylori group. Conclusions: A high percentage of spontaneous regression and complex dynamic changes in H. pylori status were observed after partial gastrectomy, especially in individ-uals with postoperative histological IM. It is better to consider postoperative eradication therapy after retesting for H. pylori. (Gut Liver 2017;11:209-215)

Using reverse docking to identify potential targets for ginsenosides

Kichul Park,Art E. Cho 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.4

Background: Ginsenosides are the main ingredients of ginseng, which, in traditional Eastern medicine, has been claimed to have therapeutic values for many diseases. In order to verify the effects of ginseng that have been empirically observed, we utilized the reverse docking method to screen for target proteins that are linked to specific diseases. Methods: We constructed a target protein database including 1,078 proteins associated with various kinds of diseases, based on the Potential Drug Target Database, with an added list of kinase proteins. We screened 26 kinds of ginsenosides of this target protein database using docking. Results: We found four potential target proteins for ginsenosides, based on docking scores. Implications of these “hit” targets are discussed. From this screening, we also found four targets linked to possible side effects and toxicities, based on docking scores. Conclusion: Our method and results can be helpful for finding new targets and developing new drugs from natural products.

Using reverse docking to identify potential targets for ginsenosides

Park, Kichul,Cho, Art E. The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.4

Background: Ginsenosides are the main ingredients of ginseng, which, in traditional Eastern medicine, has been claimed to have therapeutic values for many diseases. In order to verify the effects of ginseng that have been empirically observed, we utilized the reverse docking method to screen for target proteins that are linked to specific diseases. Methods: We constructed a target protein database including 1,078 proteins associated with various kinds of diseases, based on the Potential Drug Target Database, with an added list of kinase proteins. We screened 26 kinds of ginsenosides of this target protein database using docking. Results: We found four potential target proteins for ginsenosides, based on docking scores. Implications of these "hit" targets are discussed. From this screening, we also found four targets linked to possible side effects and toxicities, based on docking scores. Conclusion: Our method and results can be helpful for finding new targets and developing new drugs from natural products.

이산사건 시뮬레이션을 활용한 이상회로 검증 방법

신기철(Kichul Shin),박태수(Taesoo Park),박상철(Sang. C Park),왕지남(Gi. N Wang) (사)한국CDE학회 2011 한국 CAD/CAM 학회 학술발표회 논문집 Vol.2011 No.1

As we move into the late 20th century the manufacturing system has been developed continuously with automatic system. In this process, PLC (programmable Logical Controller) program has also improved the proportion of process control. However, sometimes an error can be occured the obsolete equipment or PLC due to makes the signal in put / output in the process. Because of this, if an accident occurs between facilities the accident can cause a serious problem of the production process and personal injury. At present, PLC simulation is using a direct modifying way , that fix the problem after checking a problem through a test operation in the field, because it is giving a importance to check sequence, however this way has to waste much time and manpower. Therefore, the verification technology that check a sequence or a problem is needed in the PLC simulation of the future facility process for the loss reduction and the improvement of the program quality. The objective of this research is which propose the improvement way of PLC program. If the process system use a simulation modelling a problems of process based on actual cases in the field, the simulation result can use for checking the sequence or safety circuit before actual operating process, and also it can improve of PLC program quality.

Robust query-by-singing/humming system against background noise environments

Kim, Kichul,Park, Kang Ryoung,Park, Sung-Joo,Lee, Soek-Pil,Kim, Moo Young IEEE 2011 IEEE TRANSACTIONS ON CONSUMER ELECTRONICS - Vol.57 No.2

<P>Under background noise environments, the performance of the Query-by-Singing/Humming (QbSH) system is considerably degraded. Since human pitch information is used as a feature vector for the QbSH system, a noise robust pitch estimation algorithm is inevitable. Thus, a novel pitch-estimation method is proposed by integrating temporal-autocorrelation and spectral-salience methods. As a pre-processing block, spectral smoothing is applied to enhance the stationarity of the noisy input signal. To calculate the similarity between the MIDI database and input humming signal, the dynamic time warping (DTW) algorithm is used. Jang's corpus and AURORA2 database are selected as humming and background noise signals, respectively. Compared with the standard pitch estimation algorithm in the ITU-T G.729 speech codec, the proposed pitch estimation method improves the average accuracy by 11.7% for the 0 dB signal-to-noise ratio (SNR) noise case. It also improves top-20 ratio and mean reciprocal rank (MRR) of the proposed QbSH system, on average, by 7.4% and 0.13, respectively.</P>

한자적 사고를 통한 창의적 소통

박기철(Park, Kichul) 부산울산경남언론학회 2016 지역과 커뮤니케이션 Vol.20 No.4

한자는 고리타분한 문자가 아니라 생기발랄한 문자다. 수천년 동안 한자를 사용하여 온 한민족의 우리말은 대부분 한자로 되어 있다. 순우리말처럼 여겨지는 것도 한자에서 온 낱말들이 많다. 이러한 상황에서 한자를 모르면서 외면 배격하면 스스로 외골수에 빠지는 우를 범하게 된다. 본 논문에서 제안하는 한자적 사고란 탐색적 사고, 비판적 사고, 발견적 사고다. 이 세 가지 뜻의 한자적 사고는 창의적 사고로 이어지기 쉽다. 우리가 국어생활에서 한자적 사고를 실천하다면 한자 지식도 자연스럽게 늘게 되며 결국 국어 실력이 는다. 더 나아가 생각의 근육이 키워짐에 따라 창의적 사고가 넓어지고 깊어진다. 아울러 창의력이 증진되며 결국 창의적으로 소통하는 궁극적 효과를 얻을 수 있다. Chinese characters are not old-fashioned, but full of life. Korean have used Chinese characters for thousands of years. Most Korean words are composed of Chinese characters. Lots of Korean words came from Chinese characters. Ignoring, disregarding and rejecting Chinese characters, we are single-minded. This thesis recommends Chinese characters thoughts. Chinese characters thoughts are exploratory thoughts, figurative thoughts, and heuristic thoughts. These 3 thoughts are connected with creative thoughts at last. Fulfilling Chinese characters thoughts in our Korean language life we may increase knowledge of Chinese characters, enhance ability of Korean language. Futhermore thinkig power become wider and deeper and creative power become stronger. Because our thinking muscles are raised up through Chinese characters thoughts.